A Study of Onartuzumab (MetMAb) in Combination With Bevacizumab Compared to Bevacizumab Alone or Onartuzumab Monotherapy in Participants With Recurrent Glioblastoma

NCT ID: NCT01632228

Last Updated: 2018-02-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

135 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-06-29

Study Completion Date

2016-01-21

Brief Summary

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This randomized, double-blind, placebo-controlled, multicenter phase II study will evaluate the safety and efficacy of onartuzumab in combination with bevacizumab as compared to bevacizumab alone in participants with recurrent glioblastoma. Participants will be randomized 1:1 to receive either placebo plus bevacizumab every 3 weeks, or onartuzumab plus bevacizumab. Study treatment will continue until disease progression, unacceptable toxicity, participants or physician decision to discontinue, or death.

Detailed Description

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Conditions

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Glioblastoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Onartuzumab + Bevacizumab

All participants will receive onartuzumab intravenous (IV) infusion followed by bevacizumab IV infusion every 3 weeks.

Group Type EXPERIMENTAL

Bevacizumab

Intervention Type DRUG

Participants will receive bevacizumab 15 milligrams per kilogram (mg/kg) IV infusion every 3 weeks until disease progression, unacceptable toxicity, participants or physician decision to discontinue, or death.

Onartuzumab

Intervention Type DRUG

Participants will receive onartuzumab 15 mg/kg IV infusion every 3 weeks until disease progression, unacceptable toxicity, participants or physician decision to discontinue, or death.

Placebo + Bevacizumab

All participants will receive placebo matched with onartuzumab followed by bevacizumab IV infusion every 3 weeks.

Group Type ACTIVE_COMPARATOR

Bevacizumab

Intervention Type DRUG

Participants will receive bevacizumab 15 milligrams per kilogram (mg/kg) IV infusion every 3 weeks until disease progression, unacceptable toxicity, participants or physician decision to discontinue, or death.

Placebo

Intervention Type DRUG

Participants will receive placebo matched with onartuzumab until disease progression, unacceptable toxicity, participants or physician decision to discontinue, or death.

Interventions

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Bevacizumab

Participants will receive bevacizumab 15 milligrams per kilogram (mg/kg) IV infusion every 3 weeks until disease progression, unacceptable toxicity, participants or physician decision to discontinue, or death.

Intervention Type DRUG

Onartuzumab

Participants will receive onartuzumab 15 mg/kg IV infusion every 3 weeks until disease progression, unacceptable toxicity, participants or physician decision to discontinue, or death.

Intervention Type DRUG

Placebo

Participants will receive placebo matched with onartuzumab until disease progression, unacceptable toxicity, participants or physician decision to discontinue, or death.

Intervention Type DRUG

Other Intervention Names

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MetMAb, RO5490258

Eligibility Criteria

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Inclusion Criteria

* Histologically confirmed glioblastoma at first recurrence after concurrent or adjuvant chemoradiotherapy
* Imaging confirmation of first tumor progression or regrowth as defined by RANO criteria
* Prior treatment with temozolomide
* No more than one prior line of chemotherapy
* No prior treatment with bevacizumab or other vascular endothelial growth factor (VEGF)- or VEGF-receptor-targeted agent
* No prior exposure to experimental treatment targeting either hepatocyte growth factor (HGF) or Met pathway
* No prior treatment with prolifeprospan 20 with carmustine wafer
* No prior intracerebral agent
* Recovery from the toxic effects of prior therapy
* No evidence of recent hemorrhage on baseline magnetic resonance imaging (MRI) of the brain
* No need for urgent palliative intervention for primary disease (e.g. impending herniation)
* Karnofsky performance status greater than or equal to (\>=) 70 percent (%)
* Stable or decreasing dose of corticosteroids within 5 days prior to randomization
* Prior therapy with gamma knife or other focal high-dose radiotherapy is allowed, but the participant must have subsequent histologic documentation of recurrence, unless the recurrence is a new lesion outside the irradiated field
* Participants who have undergone recent surgery for recurrent or progressive tumor are eligible provided that: surgery must have confirmed the recurrence, a minimum of 28 days must have elapsed from the day of surgery to randomization and for core or needle biopsy, a minimum of 7 days must have elapsed prior to randomization, and craniotomy or intracranial biopsy site must be adequately healed and free of drainage or cellulitis, and the underlying cranioplasty must appear intact at the time of randomization
* Availability of formalin fixed paraffin embedded tumor tissue representative of glioblastoma

Exclusion Criteria

* Pregnant or lactating women
* Inadequate hematologic, renal or liver function
* History or presence of serious cardio-vascular disease
* New York Heart Association Grade II or greater congestive heart failure
* History of another malignancy in the previous 3 years, except for in situ cancer or basal or squamous cell skin cancer
* Inadequately controlled hypertension (defined as systolic blood pressure greater than \[\>\]150 millimeter of mercury (mmHg) and/or diastolic blood pressure \>100 mmHg while on antihypertensive medication)
* Prior history of hypertensive crisis or hypertensive encephalopathy
* Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to randomization
* Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation)
* Known hypersensitivity to any excipients of onartuzumab or bevacizumab
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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University of Alabama At Birmingham; Neuro-Oncology

Birmingham, Alabama, United States

Site Status

Cedars Sinai Medical Center; Neurosurgery

Los Angeles, California, United States

Site Status

UCLA

Los Angeles, California, United States

Site Status

USCF - Neurosurgery

San Francisco, California, United States

Site Status

Stanford Comprehensive Cancer Center

Stanford, California, United States

Site Status

University of Colorado

Aurora, Colorado, United States

Site Status

Florida Cancer Specialists - Englewood

Englewood, Florida, United States

Site Status

Florida Cancer Specialists (St. Petersburg - St. Anthony's Professional Building)

St. Petersburg, Florida, United States

Site Status

Moffitt Cancer Center

Tampa, Florida, United States

Site Status

North Western Univ; Neurology

Chicago, Illinois, United States

Site Status

Northshore University Health System; Cardiology

Evanston, Illinois, United States

Site Status

Henry Ford Health System

Detroit, Michigan, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Hatton Research Institutes

Cincinnati, Ohio, United States

Site Status

Sarah Cannon Cancer Center - Tennessee Oncology, Pllc

Nashville, Tennessee, United States

Site Status

Baylor Research Inst.

Dallas, Texas, United States

Site Status

University of Virgina

Charlottesville, Virginia, United States

Site Status

Virginia Cancer Institute

Richmond, Virginia, United States

Site Status

Seattle Cancer Care Alliance; Investigational Drug Service

Seattle, Washington, United States

Site Status

Hamilton Health Sciences - Juravinski Cancer Centre

Hamilton, Ontario, Canada

Site Status

London Health Sciences Centre

London, Ontario, Canada

Site Status

Sunnybrook Health Science Centre

Toronto, Ontario, Canada

Site Status

Princess Margaret Hospital; Pencer Brain Tumour Centre, 18-727

Toronto, Ontario, Canada

Site Status

McGill University; Montreal Neurological Institute; Oncology

Montreal, Quebec, Canada

Site Status

CHUS Hopital Fleurimont; CRC

Sherbrooke, Quebec, Canada

Site Status

Hopital Avicenne; Neurologie

Bobigny, , France

Site Status

Hopital neurologique Pierre Wertheimer - CHU Lyon; Neurologie

Bron, , France

Site Status

Hopital Roger Salengro

Lille, , France

Site Status

Hopital de La Timone - CHU de Marseille; Service de neuro-oncologie - Hôpital Adultes - 12ème étage

Marseille, , France

Site Status

Centre Val Aurelle Paul Lamarque; Medecine B3

Montpellier, , France

Site Status

Hôpital Central; Departement de Neuro-Oncologie

Nancy, , France

Site Status

Hopital Pitié Salpétrière - CHU; Service de neurologie 2 - Mazarin

Paris, , France

Site Status

Ico Rene Gauducheau; Oncologie

Saint-Herblain, , France

Site Status

Hopital Purpan

Toulouse, , France

Site Status

Universitätsklinikum Bonn; Medizinische Klinik und Poliklinik I; Allgemeine Innere Medizin

Bonn, , Germany

Site Status

Universitätsklinikum Köln

Cologne, , Germany

Site Status

Klinikum Joh.Wolfg.Goethe-UNI Senckenbergisches Institut für Neuroonkologie

Frankfurt am Main, , Germany

Site Status

Universitatsklinikum Hamburg-Eppendorf; Klinik und Poliklinik fur Neurochirurgie

Hamburg, , Germany

Site Status

Ärztehaus Velen

Ibbenbühren, , Germany

Site Status

Klinikum der Johannes Gutenberg Uni Mainz; Studienz. Neurologie, Klinik und Poliklinik Neurologie

Mainz, , Germany

Site Status

Uni Klinikum München - Großhardern; Med. Klinik U. Poliklinik III - Abt. Onkologie u. Hämatologie

München, , Germany

Site Status

Pius-Hospital

Oldenburg, , Germany

Site Status

Ospedale Bellaria; U.O. Oncologia Medica

Bologna, Emilia-Romagna, Italy

Site Status

Presidio Ospedaliero Marconi Bufalini; U.O. di Oncologia

Cesena, Emilia-Romagna, Italy

Site Status

A.O. Universitaria Di Parma; Oncologia Medica

Parma, Emilia-Romagna, Italy

Site Status

Spedali Civili di Brescia

Brescia, Lombardy, Italy

Site Status

Fondazione IRCCS Ospedale Maggiore Policlinico; Gastroenterologia

Milan, Lombardy, Italy

Site Status

Fondazione IRCCS Istituto Neurologico C. Besta; Neuro-oncologia Sperimentale e Terapia Genica

Milan, Lombardy, Italy

Site Status

Azienda Ospedaliera Città della Salute e della Scienza di Torino

Turin, Piedmont, Italy

Site Status

Az. Osp. Pisana Ospedale S. Chiara; U.O. Di Reumatologia

Pisa, Tuscany, Italy

Site Status

Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia

Badalona, Barcelona, Spain

Site Status

Clinica Universitaria de Navarra; Servicio de Oncologia

Pamplona, Navarre, Spain

Site Status

Hospital Clinic i Provincial; Servicio de Farmacia

Barcelona, , Spain

Site Status

Institut Catala d Oncologia Hospital Duran i Reynals

Barcelona, , Spain

Site Status

Hospital Ramon y Cajal; Servicio de Oncologia

Madrid, , Spain

Site Status

HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia

Madrid, , Spain

Site Status

Hospital Regional Universitario Carlos Haya; Servicio de Oncologia

Málaga, , Spain

Site Status

HUG; Oncologie

Geneva, , Switzerland

Site Status

Universitätsspital Zürich; Klinik für Neurologie

Zurich, , Switzerland

Site Status

Bristol Haematology and Oncology Centre

Bristol, , United Kingdom

Site Status

Sarah Cannon Research Institute

London, , United Kingdom

Site Status

Nottingham City Hospital; David Evans Centre

Nottingham, , United Kingdom

Site Status

Countries

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United States Canada France Germany Italy Spain Switzerland United Kingdom

Other Identifiers

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2011-005912-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GO27819

Identifier Type: -

Identifier Source: org_study_id

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